We are investigating the coupling mechanisms between sensory stimuli evoked neuronal activity and plasticity-related gene expression in cortical circuits, using calcium-sensitive fluorescent dyes and genetically encoded fluorescent reporters for the activity-regulated gene Arc. Particularly, we are examining whether the induction of activity-dependent gene expression is modified under the direct influence of specific neuromodulators that are associated with the motivational or emotional relevance of a given sensory experience.[unreadable] [unreadable] We are also investigating the mechanisms by which experience-induced molecular changes impact on the subsequent cortical processing of sensory information. To this end, we are developing molecular genetic tools that would label behaviorally activated neurons in a spatially and temporally controlled manner, therefore facilitating optical tracking of activated neurons and their morphological changes. In addition, we are developing mouse genetics-based systems to optically activate or silence selected groups of neurons in order to probe their functional contributions to circuit outputs and adaptive behaviors.[unreadable] [unreadable] Finally, we are applying our opto-genetic systems to study cortical dysfunctions in the mouse models of schizophrenia as developed by the other research groups in the Genes, Cognition and Psychosis Program. In particular, by crossing transgenic mice carrying the risk alleles of candidate genes such as catechol-o-methyltransferase and potassium channel with our optical reporter and actuator lines, we can monitor the development of abnormal cortical circuits in real time, and investigate the interactions of genetic risk factors with environmental and social stressors.